Long-term changes in adipose tissue gene expression following bariatric surgery.

OBJECTIVE: Patients undergoing bariatric surgery present long-term metabolic improvements and reduced type 2 diabetes risk, despite long-term weight regain. We hypothesized that part of these protective effects could be linked to altered gene expression in white adipose tissue (WAT). METHODS: Transcriptomic profiling by gene microarray was performed in abdominal subcutaneous WAT from women before (n = 50) and two (n = 49) and five (n = 38) years after Roux-en-Y gastric bypass (RYGB) surgery as well as in 28 age-matched nonoperated women. RESULTS: In the obese women, the average body weight decrease was 38 kg 2 years postsurgery followed by an 8 kg weight regain between 2 and 5 years. Most of the long-term changes in WAT gene expression occurred during the first 2 years. However, a subset of genes encoding proteins involved in inflammation displayed a continued decrease between baseline, 2 and 5 years, respectively; that is an expression pattern independent of body weight regain. Expression of 71 of these genes correlated with measurements of adipocyte morphology or serum adipokine levels. CONCLUSION: The continuous improvement in WAT inflammatory gene expression, despite body weight relapse, may contribute to the sustained effects on adipose morphology after bariatric surgery.

Epigenetic regulation of diabetogenic adipose morphology.

OBJECTIVE: Hypertrophic white adipose tissue (WAT) morphology is associated with insulin resistance and type 2 diabetes. The mechanisms governing hyperplastic versus hypertrophic WAT expansion are poorly understood. We assessed if epigenetic modifications in adipocytes are associated with hypertrophic adipose morphology. A subset of genes with differentially methylated CpG-sites (DMS) in the promoters was taken forward for functional evaluation. METHODS: The study included 126 women who underwent abdominal subcutaneous biopsy to determine adipose morphology. Global transcriptome profiling was performed on WAT from 113 of the women, and CpG methylome profiling on isolated adipocytes from 78 women. Small interfering RNAs (siRNA) knockdown in human mesenchymal stem cells (hMSCs) was used to assess influence of specific genes on lipid storage. RESULTS: A higher proportion of CpG-sites were methylated in hypertrophic compared to hyperplastic WAT. Methylation at 35,138 CpG-sites was found to correlate to adipose morphology. 2,102 of these CpG-sites were also differentially methylated in T2D; 98% showed directionally consistent change in methylation in WAT hypertrophy and T2D. We identified 2,508 DMS in 638 adipose morphology-associated genes where methylation correlated with gene expression. These genes were over-represented in gene sets relevant to WAT hypertrophy, such as insulin resistance, lipolysis, extracellular matrix organization, and innate immunity. siRNA knockdown of ADH1B, AZGP1, C14orf180, GYG2, HADH, PRKAR2B, PFKFB3, and AQP7 influenced lipid storage and metabolism. CONCLUSION: CpG methylation could be influential in determining adipose morphology and thereby constitute a novel antidiabetic target. We identified C14orf180 as a novel regulator of adipocyte lipid storage and possibly differentiation.

Assessment of vertigo.

Vertigo is defined as a subjective sense of imbalance and includes unsteadiness as well as a sensation of rotation. Vertiginous symptoms may arise from defects in the labyrinth, the visual system, or the central nervous system, although in most patients presenting with balance problems, the lesion lies within the labyrinth or its central connections. The most important step in the diagnosis is an unhurried and detailed history, bearing in mind that many patients will have difficulty in describing their symptoms. A detailed neurological examination is usually unnecessary but one must examine the ears, cranial nerves, cerebellum, and balance function, and look for the presence of nystagmus. The common error of carrying out investigations in place of a detailed history is to be avoided. In many cases, investigations are not required at all, although it is the author's practice to do a routine pure tone audiogram with basic assessment of speech discrimination. There is no indication for routine caloric testing, imaging or blood analysis, each of which should be carried out only when there are specific indications. In the routine clinical care of patients, it is only in exceptional situations that specialised vestibular testing is required, although these are often necessary in research projects.

Management of otoscierosis--an Irish perspective.

The last 30 years have seen a gradual change in the management of otosclerosis. The aim of this study is to evaluate the current practice amongst Irish otolaryngology consultants by a questionnaire and to compare it with the practice currently followed in Great Britain. Thirty-eight responses (67.9%) were available for analysis. The overall trend is towards centralisation with a reduction in the number of surgeons undertaking stapes surgery (39%). The majority of consultants (67%) who undertake stapes surgery would operate for a unilateral conductive loss and 67% would undertake bilateral stapes surgery. Stapedotomy is the only operation performed (100%) with none of the consultants performing partial or total stapedectomies.

Management of otosclerosis in the UK.

The last 30 years has seen a gradual change in the management of otosclerosis. The aim of this study is to evaluate the current practice among British otolaryngology consultants using a questionnaire, and to compare it with the practice reported in a survey 8 years ago. A total of 353 valid responses (64.5%) were available for analysis. The overall trend is towards centralization, with a reduction in the number of surgeons undertaking stapes surgery (49.9%). The majority of consultants (81.3%) who undertake stapes surgery would operate for a unilateral conductive loss and 75.1% would undertake bilateral stapes surgery. Stapedotomy is the operation of choice (82%), with a few consultants performing partial or rarely total stapedectomies. Postoperative restrictions and follow-up times vary widely amongst surgeons, with the senior surgeons tending to be more conservative than the younger consultants.

Artificial tympanic membrane and ossiculoplasty.

We report an unusual case of a subjective hearing improvement, confirmed by audiometry, in a patient using a paper towel prosthesis.

Disintegration of porous polyethylene prostheses.

A Plastipore (porous polyethylene) Total Ossicular Replacement Prosthesis gave an excellent initial hearing result which was maintained for 14 years. Hearing then began to deteriorate and revision surgery showed disintegration of the prosthesis and a defect in the stapes footplate. Histological examination confirmed previous findings in porous polyethylene with multinucleated foreign body giant cells and breakdown of the material.

Streptomycin perfusion of the labyrinth in the treatment of Menière's disease: a modified technique.

The ideal surgical procedure for Menière's disease would combine the high rate of vertigo control and the good hearing preservation of vestibular nerve section with the low morbidity of labyrinthectomy. Shea's technique of streptomycin perfusion of the labyrinth has been modified by making an additional opening into the posterior semicircular canal in an effort to limit the amount of streptomycin going into the cochlea. Seventeen patients with definite Menière's with poor hearing have had this procedure. Vertigo was controlled in 94% and the hearing preserved in 55%. Vestibular rehabilitation was not a problem. It is speculated that hearing preservation would be better if the procedure were not restricted to those with poor hearing. This method of destruction of the vestibular system carries the possibility of hearing preservation and maintains the possibility of cochlear implantation should this ever be required.

A new approach to surgery for Menière's disease: talking about surgery.

Many patients experience a remission of their Menière's disease between the time that surgery is agreed and their admission to hospital for the procedure. In a series of 23 consecutive patients where surgery appeared to be indicated for control of the vertigo of Menière's disease, 12 settled within 6-8 weeks of agreeing that something would be done, and thereby avoided any surgical procedure. It is suggested that these patients may have been experiencing the same effect as provided by the conservative surgical procedures. In the absence of any clear evidence for a specific surgical effect from any conservative operation for Menière's disease, the authors put forward the suggestion that abandoning all the conservative procedures in favour of the protocol of planned surgery should be considered; wait for 2 months and, if the incapacitating episodic dizziness continues, one should proceed to a differenting procedure.

Small vestibular schwannomas in the elderly: a management dilemma.

Small vestibular schwannomas were diagnosed in two elderly patients and, for different reasons, a policy of watch and wait was instituted. One was reliable in attending for follow-up and lived for over 20 years without surgical intervention. The other was unreliable in follow-up, there was an unexpected and undetected acceleration of the growth rate and urgent surgery became imperative at the age of 77 years. This provided to be unsuccessful. A watch and wait policy is acceptable in the elderly but only if the patient can be relied upon to co-operate in follow-up attendance and imaging.

Long-term results of vestibular nerve section.

Records are available on 27 patients who had vestibular nerve section between 1975 and 1987 giving a follow-up time of 10 to 22 years with a mean of 16 years. Episodic vertigo was fully controlled in 26 patients, one needing a labyrinthectomy 18 months later. In addition to the patient who had labyrinthectomy, one patient had immediate post-operative profound hearing loss so that long-term follow-up of hearing was possible in 25 patients. After six months there was an overall average improvement in hearing of 1 dB. Thereafter there were average deterioration of 7 dB at two years, 15 dB at 10 years, 23 dB at 15 years and 29 dB at 20 years. This deterioration was more marked in those who had better hearing at the time of surgery, with all 10 whose hearing was classified as good deteriorating to poor by 15 years. At 10 years hearing deteriorated by 25 dB in those with good hearing and by 7 dB in those with poor hearing. In 20 per cent of patients there was audiological evidence of eventual involvement of the other ear. Tinnitus became worse in five patients but was a major problem in only one patient. One patient suffered a facial paralysis with partial recovery and, in addition, in one the frontal branch was divided in the incision.

The anterior hitch method of tympanic membrane repair.

Anterior perforations of the tympanic membrane have been previously shown to have a higher failure rate than others following tympanoplasty procedures. A technique has been previously described utilizing an anterior hitch graft stabilization with avoidance of anterior blunting of the tympanic membrane. Follow-up cases in which this technique has been utilized show greatly improved results in terms of perforation closure.

Disability after labyrinthectomy.

A labyrinthectomy is known to relieve vertigo successfully in the majority of patients who suffer from Menière's disease and have non-serviceable hearing in the affected ear. It is assumed that the procedure reduces disability, helps the patient to return to work and improves the quality of life. Eighteen patients who underwent a transmastoid drill-out labyrinthectomy between 1980 and 1990 were interviewed and an attempt was made to evaluate the success of the operation in accordance with the guidelines set out by the AAO-HNS 1985. In the present series it was noted that although vertigo was relieved in 89 per cent of patients after labyrinthectomy, only 50 per cent of them returned to work. In this study, the age and occupation of the patient at the time of surgery and the relief of vertigo did not accurately predict whether or not a patient returned to work.

Syphilitic labyrinthitis--an update.

Forty-eight patients with syphilitic labyrinthitis have been treated and followed up for periods of six months to 25 years; interpretation of the hearing results must be in the light of the natural history of this condition which is perceived to be progression of hearing loss to profound deafness. At the beginning of the series treatment was with ampicillin alone and on this treatment 11 ears with useful hearing were maintained at this level. The group with combined ampicillin and prednisone treatment, which included some failures from ampicillin alone, maintained useful hearing in 28 out of 29 ears. Those treated initially with ampicillin and prednisone and later also given regular injections of ACTH, maintained hearing in 16 out of 17 ears. At the outset, there were 29 profoundly deaf ears. One of these recovered some useful hearing but two ears with useful hearing at the outset became profoundly deaf so that at the end there were 30 profoundly deaf ears. However, all patients as opposed to ears, with useful hearing at the outset were left with some hearing; no patient became profoundly deaf.

Bilateral acoustic neuromas.

This article reviews 12 patients with bilateral acoustic neuromas. The sex incidence was equal and the mean age at diagnosis was 26.2 years. The family history was positive in nine of the patients. Five patients have had incomplete surgical removal of acoustic neuromas on both sides. Two of them are completely deaf and the other three have severe sensorineural hearing loss in one ear and no hearing in the other ear. In five patients the tumour on one side has been operated on and the other side is being observed with at least short-term preservation of good hearing. The remaining two patients died of intra-cranial complications, one of them post-operatively. Four patients developed facial palsy immediately following surgery and one developed facial weakness 6 months after surgery. Guidelines are discussed for the care of these patients including the timing of surgery and alternative treatment options (observation, radio-surgery and chemotherapy). This is essentially a group of young individuals who have had multiple operations for bilateral acoustic tumours and associated manifestations and for whom the disease and the sequelae of treatment can be tragic.